Diffusion and concentration profiles of drugs in gels

A versatile membraneless method was used to study the diffusion of acetaminophen, ibuprofen, indomethacin, theophylline, and chlorpheniramine in thermoreversible gels. Two independent ways to calculate the diffusion coefficients and to verify Fickian transport are presented; the most sensitive criterion for Fickian transport being an agreement between the concentration profile for the drug in the gel and the free diffusion model. The diffusion of acetaminophen, ibuprofen, and indomethacin was studied at different temperatures in 1% (w/w) agarose gels. The diffusion coefficients for these drugs were found to be essentially the same as in water, and the apparent diffusion activation energies are close to that for self diffusion of water (4.62 kcal/mol), indicating a common mechanism for the diffusion of these drugs in the gel. The diffusivity of chlorpheniramine was also studied in 4% (w/w) agarose gels or with part of the agarose substituted with other polymers (e.g., chitosan and sodium alginate). These two oppositely charged polymers, mixed together, were found to occupy an "equivalent polymer volume" that was three times larger than the same amount of each of the constituents. When chitosan and gelatin-B were mixed into the agarose gel, non-Fickian transport resulted. Such non-Fickian transport was also observed with theophylline diffusing in a mixture of agarose, chitosan, and sodium alginate at a low pH.